Blood treatment systems

ABSTRACT

Dialyzer systems can consolidate multiple technologies and functionalities of blood treatment systems in a significantly integrated fashion. For example, this disclosure describes dialyzer systems that include a magnetically driven and magnetically levitating pump rotor integrated into the dialyzer. Such a dialyzer can be used with treatment modules that include a magnetic field-generating pump drive unit. In some embodiments, the dialyzers include pressure sensor chambers with flexible membranes with which corresponding pressure transducers of the treatment modules can interface to detect arterial and/or venous pressures.

CLAIM OF PRIORITY

This application claims priority under 35 USC § 119(e) to U.S. PatentApplication Ser. No. 62/934,260, filed on Nov. 12, 2019, the entirecontents of which are hereby incorporated by reference.

TECHNICAL FIELD

This invention relates to blood treatment systems and methods used forextracorporeal blood treatment procedures.

BACKGROUND

Renal dysfunction or failure and, in particular, end-stage renaldisease, causes the body to lose the ability to remove water andminerals, maintain acid-base balance, and control electrolyte andmineral concentrations within physiological ranges. Toxic uremic wastemetabolites, including urea, creatinine, and uric acid, accumulate inthe body's tissues which can result in a person's death if thefiltration function of the kidney is not replaced.

In treating chronic renal failure, various methods of purification andtreatment of blood with machinery are used for removing substancesusually eliminated with the urine and for withdrawing fluids. Diffusemass transport is predominant in hemodialysis (HD), while inhemofiltration (HF) convective mass transport through a membrane isused. Hemodiafiltration (HDF) is a combination of the two methods.

During HD, blood passes from the patient through a dialyzer thatincludes a semi-permeable membrane to separate the blood from a largevolume of externally-supplied dialysis solution, also referred to asdialysate. The waste and toxins, including excess fluids, dialyze out ofthe blood through the semi-permeable membrane into the dialysate, whichis then typically discarded. The transportation of the small molecularsubstances through the semi-permeable membrane is determined mainly bythe differences in concentration between the dialysate and the blood.The dialysate is referred to as “fresh dialysate” prior to receiving thedialyzed components of the blood, and the dialysate that exits thedialyzer after receiving the dialyzed components is referred to as“spent dialysate.”

During HDF, part of the serum withdrawn through the semi-permeablemembrane is replaced by a sterile substitution fluid which is passed tothe extracorporeal blood stream either upstream of the dialyzer ordownstream of the dialyzer. The supply of substitution fluid upstream ofthe dialyzer is also referred to as pre-dilution, and the supplydownstream of the dialyzer is also referred to as post-dilution.

SUMMARY

Dialyzer systems described herein can include a magnetically driven andmagnetically levitating pump rotor integrated into the dialyzer. Such adialyzer is configured for use with treatment modules described hereinthat include a magnetic field-generating pump drive unit. In someembodiments, the dialyzers include pressure sensor chambers withflexible membranous walls against which corresponding pressuretransducers of the treatment modules can interface to detect arterialand/or venous pressures. Additional features, as described herein, canbe incorporated into the dialyzers and treatment modules to consolidatecomponents, simplify setup, and enhance blood treatment performance.

In one aspect, the disclosure is directed to a dialyzer. The dialyzerincludes an elongate housing defining a longitudinal axis and includingfirst and second end caps at opposite ends of the housing. A pluralityof hollow membranous fibers are located within an interior of thehousing between the first and second end caps. Each hollow membranousfiber defines a lumen. The dialyzer defines a blood flow path thatextends through the first end cap, then through the lumens of the hollowmembranous fibers, and then through the second end cap. The blood flowpath enters the first end cap transverse to the longitudinal axis, thenextends toward the hollow membranous fibers and through openings definedby the first end cap prior to entering the lumens of the hollowmembranous fibers.

Such a dialyzer may optionally include one or more of the followingfeatures in any combination(s). A portion of the blood flow path withinthe first end cap may extend transverse to the longitudinal axis. Theblood flow path within the first end cap may also include blood flowpath portions that extend in opposite directions along the longitudinalaxis. The first end cap may redirect the blood flow path that extendstransverse to the longitudinal axis to extend parallel to thelongitudinal axis toward the hollow membranous fibers. In someembodiments, the first end cap defines a toroidal space. The first endcap may include an internal annular concave wall surface that defines aportion of the toroidal space. The toroidal space and/or the internalannular concave wall surface may surround a pump rotor located withinthe first end cap. In some embodiments, the first end cap defines atleast two of the openings. The blood flow path may enter the first endcap between the openings and the hollow membranous fibers. The dialyzermay also include a check valve along the blood flow path. In someembodiments, the second end cap includes a port along the blood flowpath for administering medicaments or extracting a fluid sample. Thehousing may also include a deaeration chamber along the blood flow path.The deaeration chamber may be defined in the second end cap. Theopenings may include at least two arcuate slots. In some embodiments,the openings may include at least four arcuate slots. The dialyzer mayalso include a pump rotor within the housing. The pump rotor may bemagnetically-drivable to force fluid (e.g., blood) through the housingand/or through lumens of a plurality of hollow membranous fibers withinthe housing. The dialyzer may also include an arterial pressuredetection chamber arranged between a blood inlet defined by the firstend cap and the hollow fibers. The arterial pressure detection chambermay have a first flexible surface. The first flexible surface may beattached to the first end cap. The first end cap may define a firstdialysate port. The dialyzer can also include a venous pressuredetection chamber arranged in the second end cap between the hollowfibers and a blood outlet defined by the second end cap. The venouspressure detection chamber can have a second flexible surface. Thesecond flexible surface may be attached to the second end cap.

Embodiments can include one or more of the following advantages.

In some embodiments, multiple technologies and functionalities of bloodtreatment systems are consolidated in a significantly refined andintegrated fashion into the dialyzer and treatment module systemsdescribed herein. For example, in some embodiments a single dialyzerunit as described further below can replace significant portions of aconventional hollow-fiber dialyzer, tubing set, air removal system,sample port, and pump. Moreover, the end caps of some dialyzersdescribed herein can include accessible pressure chambers with flexiblemembranous walls for convenient measuring of arterial and venouspressures in a non-invasive manner. In some embodiments, the end caps ofthe dialyzers can include (a) a port to receive fresh dialysate fluidfrom the treatment module and (b) a port to return spent dialysate fluidto the treatment module after passing over the dialysis membrane. Insome embodiments, the end caps of the dialyzers can also include portsby which substituate liquid can be directly added to the blood prior toand/or after the blood passes through the hollow fiber blood treatmentsection of the dialyzer. Additionally, in some embodiments, the samedialyzer and treatment module systems are configured for carrying outany of multiple different types of blood treatments, including, forexample, HD and HDF.

In contrast to typical HD and HDF machines, some example embodimentsreduce the number of required setup steps, which may result in reducedsetup time and reduced opportunity for human error. In a clinic setting,this can free up valuable nursing resources and streamline patient care.This simplification can free up nursing or other personnel resources ina clinic or home setting, and also makes the process easier and morefeasible for patients to set up the dialysis machine themselves.

In some embodiments, the consolidated dialyzer and treatment modulesystems described herein, provide important functional advantages. Forexample, the consolidation can reduce the amount of tubing needed forthe extracorporeal circuit to be used for a blood treatment session.Moreover, the treatment module can be mounted on an arm extending from ablood treatment machine console so that the treatment module anddialyzer can be located very close to a patient. These features allowthe length of extracorporeal tubing needed for a blood treatment sessionto be significantly minimized. Accordingly, the volume of primingsolution required is advantageously reduced. Additionally, exposure ofthe patient's blood to contact with foreign surfaces is alsoadvantageously reduced. The consolidated form factor also gives rise toadditional advantages such as less potential for leaks, less hemolysis,less biohazard waste, less packaging waste, and reduced transportationexpenses.

In some embodiments, a magnetic pump rotor is integrated to the dialyzerin a liquid-tight manner. Such an integrated pump rotor can bebearing-less, magnetically levitated, and rotationally driven by anexternal pump drive unit that generates dynamic magnetic fields. Thisarrangement provides advantages such as lower hemolysis as compared toconventional pumping systems used for extracorporeal blood treatments,and a bearing-free design that reduces system maintenance requirementsand the potential for contamination. Moreover, since the pump drive unitand pump rotor are separated, easier cleaning of machine interfaces isadvantageously facilitated.

In some embodiments, the consolidated dialyzer and treatment modulesystems described herein are also easier to set-up and use as comparedto conventional systems. Accordingly, set-up times can be reduced andpotential for errors can be mitigated. In result, the treatment costsper patient can be reduced in some embodiments.

The details of one or more embodiments are set forth in the accompanyingdrawings and the description below. Other aspects, features, andadvantages will be apparent from the description and drawings, and fromthe claims.

DESCRIPTION OF DRAWINGS

FIG. 1 depicts a patient receiving an extracorporeal blood treatmentusing a blood treatment system.

FIG. 2 is an exploded perspective view of a dialyzer and treatmentmodule system of the blood treatment system of FIG. 1 .

FIG. 3 is a perspective view of the dialyzer and the treatment modulesystem of FIG. 2 in an assembled configuration.

FIG. 4 is a schematic depiction of the dialyzer of the blood treatmentsystem of FIG. 1 , showing the blood flow path through the dialyzer.

FIG. 5 is another schematic depiction of the dialyzer of the bloodtreatment system of FIG. 1 , showing the blood flow path through thedialyzer and substituate addition locations.

FIG. 6 is another schematic depiction of the dialyzer of the bloodtreatment system of FIG. 1 , showing the dialysate flow path through thedialyzer.

FIG. 7 is another schematic depiction of the dialyzer of the bloodtreatment system of FIG. 1 , showing the blood and dialysate flow pathsand the substituate addition locations.

FIG. 8 is a rear view of the dialyzer of the blood treatment system ofFIG. 1 .

FIG. 9 is a front view of the dialyzer of the blood treatment system ofFIG. 1 .

FIG. 10 is a side view of the dialyzer of the blood treatment system ofFIG. 1 with the arterial and venous lines shown in section.

FIG. 11 is a top view of the dialyzer of the blood treatment system ofFIG. 1 with the arterial and venous lines shown in section.

FIG. 12 is a cross-sectional view of the dialyzer of the blood treatmentsystem of FIG. 1 taken along section line A-A of FIG. 10 .

FIG. 13 is a broken cross-sectional view of the dialyzer of the bloodtreatment system of FIG. 1 taken along section line B-B of FIG. 11 .

FIG. 14 is a cross-sectional view of the second end cap of the dialyzerof the blood treatment system of FIG. 1 taken along section line C-C ofFIG. 11 , with the position of a dialyzer potting shown in broken lines.

FIG. 15 is a cross-sectional view of the dialyzer of the blood treatmentsystem of FIG. 1 taken along section line D-D of FIG. 10 .

FIG. 16 is a cross-sectional view of the dialyzer of the blood treatmentsystem of FIG. 1 taken along section line E-E of FIG. 10 .

FIG. 17 is a broken cross-sectional view of the dialyzer of the bloodtreatment system of FIG. 1 taken along section line B-B of FIG. 11 ,with the bundle of hollow fibers and the pottings shown in broken lines.

FIG. 18 is a cross-sectional view of the dialyzer of the blood treatmentsystem of FIG. 1 taken along section line F-F of FIG. 10 .

FIG. 19 is a cross-sectional view of the dialyzer of the blood treatmentsystem of FIG. 1 taken along section line G-G of FIG. 10 .

FIG. 20 is a perspective view of a first end cap of the dialyzer of theblood treatment system of FIG. 1 .

FIG. 21 is a rear view of the first end cap of FIG. 20 .

FIG. 22 is another perspective view of the first end cap of FIG. 20 .

FIG. 23 is a perspective view of the first end cap of FIG. 20 shown in apartial longitudinal cross-sectional view and depicting blood flowtherethrough.

FIG. 24 is a perspective view of a pump rotor that is configured to belocated in the first end cap of FIG. 20 .

FIG. 25 is a perspective view of an alternative pump rotor that can beused in the first end cap of FIG. 20 .

FIG. 26 is a perspective view of a second end cap of the dialyzer of theblood treatment system of FIG. 1 .

FIG. 27 is a rear view of the second end cap of FIG. 26 .

FIG. 28 is another perspective view of the second end cap of FIG. 26 .

FIG. 29 is a cross-sectional view of an alternative second end cap.

FIG. 30 is a perspective view of the treatment module of the bloodtreatment system of FIG. 1 in a first configuration.

FIG. 31 is a perspective view of the treatment module of FIG. 30 in asecond configuration.

FIG. 32 is an exploded perspective view showing the first end cap ofFIG. 20 and a first pressure sensor and a first pair of conduits of thetreatment module of FIG. 30 .

FIG. 33 is a top perspective view of the first end cap, the firstpressure sensor, and the first pair of conduits of FIG. 32 shown in aseparated configuration.

FIG. 34 is a top perspective view of the first end cap, the firstpressure sensor, and the first pair of conduits of FIG. 32 shown in anoperative, coupled configuration.

FIG. 35 is a perspective view of an alternative treatment module.

FIG. 36 is a perspective view of an alternative first (arterial) end capshown in a partial longitudinal cross-sectional view.

FIG. 37 is a rear view of an example dialyzer that is configured similarto the dialyzer of the blood treatment system of FIG. 1 , except withoutHDF capability.

FIG. 38 is a front view of the dialyzer of FIG. 37 .

FIG. 39 is a side view of the dialyzer of FIG. 37 .

FIG. 40 is a longitudinal cross-sectional view of an alternative second(venous) end cap.

FIG. 41 is a perspective view showing a portion of the venous end cap ofFIG. 40 .

FIG. 42 is a perspective view of a portion of another alternative second(venous) end cap.

FIG. 43 is a longitudinal cross-sectional view of the venous end cap ofFIG. 42 .

FIG. 44 is another perspective view of the venous end cap of FIG. 42 .

FIG. 45 is a longitudinal cross-sectional view of another alternativesecond (venous) end cap. The venous end cap is shown in a firstconfiguration.

FIG. 46 is a longitudinal cross-sectional view of the venous end cap ofFIG. 45 in a second configuration.

FIG. 47 is a perspective view showing a portion of the venous end cap ofFIG. 45 .

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

This disclosure describes dialyzer systems that can include amagnetically driven, magnetically levitating pump rotor integrated intothe dialyzer. Such a dialyzer can be used with treatment modulesdescribed herein that include a dynamic magnetic field-generating pumpdrive unit. In some embodiments, the dialyzer includes one or morepressure sensor chambers with flexible exterior membrane walls withwhich corresponding pressure transducers of the treatment modulesinterface to detect arterial and/or venous pressures. The dialyzersystems described herein consolidate multiple diverse technologies andfunctionalities of blood treatment systems in a significantly integratedfashion to consolidate components, reduce costs, simplify setup, andenhance performance.

With reference to FIG. 1 , a patient 10 is depicted as receiving anextracorporeal blood treatment using a blood treatment system 1 thatincludes a disposable set connected to a blood treatment machine 200.The disposable set includes a dialyzer 100 that is coupled to atreatment module 220 of the blood treatment machine 200. In some cases,the patient 10 may receive treatment for a health condition such asrenal failure. Accordingly, the system 1 can be used to provide one ormore types of treatment to the patient 10, including hemodialysis (HD),hemodiafiltration (HDF), or some other type of blood treatment. For suchtreatments, blood is withdrawn from the patient 10 via an arterial line102 and, after passing through the dialyzer 100, treated blood isreturned to the patient 10 via a venous line 104. The dialyzer 100 is asingle-use disposable item, whereas the blood treatment machine 200 is adurable reusable system. In some cases, a single dialyzer 100 may bereused two or more times for a particular individual patient.

The blood treatment machine 200 includes a blood treatment machineconsole 210, the treatment module 220, and an arm 280 that connects thetreatment module 220 to the blood treatment machine console 210. The arm280 extends from the blood treatment machine console 210, and thetreatment module 220 is mounted to the other end of the arm 280. Inother words, the treatment module 220 is cantilevered from the bloodtreatment machine console 210 by the arm 280.

The arm 280 includes one or more adjustable joints so that the arm 280can be manually articulated to position the treatment module 220 invarious positions/orientations relative to the blood treatment machineconsole 210 and/or relative to the patient 10. For example (as depictedin FIG. 1 ), in some cases the arm 280 can be extended so that thetreatment module 220 is positioned close to the patient 10. Accordingly,the arterial line 102 and the venous line 104 can be quite short ascompared to conventional blood treatment systems. For example, in someembodiments, the arterial line 102 and the venous line 104 have a lengthless than one meter (e.g., less than 90 cm, less than 80 cm, less than70 cm, less than 60 cm, less than 50 cm, less than 40 cm, less than 30cm, or less than 20 cm).

In some embodiments, the treatment module 220 and/or the arm 280 caninclude one or more sensors 226 that output signals that can indicatethe position, orientation, and/or motion of the treatment module 220relative to the blood treatment machine console 210. For example, insome cases sensors such as accelerometers (e.g., 3D accelerometers),gyroscopic sensors, ultrasonic sensors, proximity sensors, opticalsensors, magnetometers, global positioning sensors, radio triangulationsensors (e.g., like in keyless access systems for cars or based on WiFi,Bluetooth or similar technologies), electronic spirit levels, electricspirit levels, and/or the like, within the treatment module 220 and/orthe arm 280 may be utilized to indicate the position, orientation,and/or motion of the treatment module 220 relative to the bloodtreatment machine console 210.

In some embodiments, the signal output(s) from such sensors 226 can beused by the control system of the blood treatment system 1 as input(s),for example, to activate or deactivate certain modes of operation of theblood treatment system 1 or, alternatively, to determine the currentsituation of the treatment module 220. For example, a certainorientation of the treatment module 220 might be used to indicate that amaintenance mode should be activated. Pulling the treatment module 220forward, towards the patient, might initiate preparations for atreatment mode. Another particular orientation of the treatment module220 might be defined as indicative for activating a deaeration mode.Pushing back the treatment module 220 toward the blood treatment machineconsole 210 might act as input for pausing operation of the bloodtreatment system 1, and so on. Other modes of operation of the bloodtreatment system 1 that can be activated in response to a particularposition, orientation, or motion of the treatment module can include,but are not limited to, a “nurse mode,” a debugging mode, and a fillingor priming mode, to provide a few examples. Including the one or moresensors 226 that output signals that can indicate the position,orientation, and/or motion of the treatment module 220 relative to theblood treatment machine console 210 allows user control interactionswith the blood treatment system 1, conveniently and intuitively, by themanual handling of the arm-mounted treatment module 220. The electronicsand/or controls that receive and interpret output signals from thesensors 226 can be located in the blood treatment machine console 210,the treatment module 220, the arm 280, and/or elsewhere. In someembodiments, the raw data from one or more sensors 226 is/are processedin a separate step to generate the sensor output that is used in furthersteps. In some embodiments, the processor carrying out this processingstep is located in the treatment module 220. In some embodiments, theprocessor carrying out this processing step is located in the arm 280.In some embodiments, the processor carrying out this processing step islocated in the blood treatment machine console 210.

In some embodiments, there are additionally or alternatively sensorslocated in the arm 280 to determine the position and/or orientation ofthe treatment module 220. Such sensors can be angle sensors, pathsensors, range sensors, and/or other types of sensors. In someembodiments, such sensors can be used to recognize if a situation ofmechanical shock has occurred, such as in case of a mechanical impact ofa person or an object making contact with the treatment module 220. Thedetection of the impact event can be used to identify alarms as falsealarms, when they occur at the same time in other sensors triggered bythe impact event. For example, an ultrasonic air bubble detector couldproduce sensor readings causing an alarm in case of an impact event. Theaccelerometer or position sensor(s) in the treatment module 220 and/orarm 280 could enable detecting an impact event that occurred at the timeof that alarm. In this case, the treatment module controls coulddeescalate that alarm taking into account the air bubble detectorreadings would likely have been be falsified due to the detected impactevent.

Further advantages of the using such sensors as described above include,in combination with a de-aeration mode or priming mode, utilizing thesensor readout for initiating a certain operating state to reduce thework load for personnel handling the a treatment module 220.Additionally, the haptic input channel would allow for a more intuitiveway of handling the treatment module 220. Further, these concepts canhelp avoid errors and mistakes in handling and treatments, and falsealarms can be identified.

In some embodiments, the output signal(s) from the sensor(s) 226 may beguided to a control unit in the treatment module 220, and/or the console210, and the control unit may be configured or programmed to disable orenable predefined processes of the blood treatment system 1 on the basisof the signal(s). In some embodiments, the priming phase of the dialyzer100 (which means filling the dialyzer 100 with liquid and deaerating thedialyzer 100) and/or the treatment phase of the blood treatment system 1is only enabled when the signal indicates a vertical position of thedialyzer 100. In some embodiments, the signal(s) from the sensor(s) 226must indicate that treatment module 220 is in an angled position inrelation to the ground (level in relation to the earth), so that anyliquid that could flow out of the liquid circuit is not dropping to theearth but conducted along the surface of the treatment module 220 andmay be guided into a liquid collection port of the treatment module 220.The liquid collection port may by a rail along the lower end of thetreatment module 220 and being connected to a container to collectleaking liquid.

The control unit may further be connected to a user interface, such asthe user interface 212. The user interface may be a graphical userinterface and optical light system, a sound generating system, or anycombination thereof. The user interface may be configured to display theorientation of the treatment module 220 (as provided by the signal(s)from the sensor(s) 226) and the display may change in visible appearanceas a function of the enabled processes.

In one example embodiment, the graphical user interface will show theorientation of the treatment module 220 when the next process step is,for example, the priming phase. Only if the treatment module 220 is inthe upright position 220 (as detected by the signal(s) from thesensor(s) 226) will the orientation be displayed in green and theoperator will be able to manually initiate the priming phase via userinterface actions (e.g., speech, button, gesture, etc.), or the systemwill automatically initiate the next process step.

Although the illustrated example includes a treatment module 220 that ismoveable relative to the base console 210, it should be understood thatsome other examples do not include a separately positionable treatmentmodule 220. In such examples, the base console 210 may incorporate thefeatures described with respect to the illustrated treatment module 220other than those specific to the positionability.

The blood treatment machine console 210 includes a user interface 212, acontrol system, facilities for making dialysate, and the like.

In the blood treatment system 1, much of the componentry associated withconventional systems is incorporated into the dialyzer 100 and portionsof the blood treatment module 220 that interfaces with the dialyzer 100.Conventional blood treatment systems generally include a disposabletubing set and/or cassette (in addition to a dialyzer). Such a tubingset and/or cassette is used to interface with one or more hardware itemssuch as pumps, sensors, valve actuators, and the like. However, thedialyzer 100 and the blood treatment machine 200 integrate multiplefunctionalities in a highly consolidated fashion (as described furtherbelow).

Referring also to FIGS. 2 and 3 , the dialyzer 100 is releasablycoupleable to the treatment module 220 in a convenient manner. Forexample, in the depicted embodiment, the dialyzer 100 is slidablycoupleable with the treatment module 220. Accordingly, the dialyzer 100and treatment module 220 include complementary structural features tofacilitate slidable coupling. That is, the dialyzer 100 includes a firstprojection 106 that is slidably coupleable with a first complementarilyshaped slot 222 of the treatment module 220, and the dialyzer 100includes a second projection 108 that is slidably coupleable with asecond complementarily shaped slot 224 of the treatment module 220. Insome embodiments, other means of releasably connecting the dialyzer 100to the treatment module 220 can be used. For example, in someembodiments a connection style such as a snap-in connection, a thumbscrew connection, a clamp connection, a suction connection, and the likecan be used.

The dialyzer 100 includes a housing 110 that defines an interior space.A bundle of hollow fiber semi-permeable membranes (or simply “hollowfibers”) are disposed within the interior of the housing 110. Thearterial line 102 and the venous line 104 each extend from the housing110 (e.g., from opposite ends of the housing 110) and are in fluidcommunication with the interior of the housing 110, and with lumens ofthe hollow fibers.

The housing 110 includes a first end cap 120 and a second end cap 140.The first end cap 120 includes the first projection 106 and the secondend cap 140 includes the second projection 108. Moreover, the arterialline 102 is coupled to the first end cap 120 and the venous line 104 iscoupled to the second end cap 140.

The treatment module 220 includes a pump drive unit 230 that isconfigured to releasably receive a portion of the first end cap 120. Asdescribed further below, the pump drive unit 230 generates dynamicmagnetic fields to levitate and rotate a pump rotor that is housedwithin the portion of the first end cap 120. In some embodiments, thepump drive unit 230 includes no moving parts.

The pump rotor is configured such that rotation of the pump rotor forcesblood of the patient 10 through the lumens of the hollow fibers of thedialyzer 100 in the direction from the first end cap 120 toward thesecond end cap 140. Accordingly, blood from the patient 10 flows intothe dialyzer 100 via the arterial line 102, flows through the lumens ofthe hollow fibers, and flows out of the dialyzer 100 via the venous line104.

The treatment module 220 also includes other devices that interface withthe arterial line 102 and/or the venous line 104. For example, thedepicted treatment module 220 includes a tubing interface module 240configured to releasably receive a portion of the arterial line 102and/or a portion of the venous line 104. The tubing interface module 240can include devices that can perform functions such as flow ratedetection, gaseous bubble detection, and the like. That is, the tubinginterface module 240 can include sensors for detecting one or moreparameters such as a flow rate of the blood within the arterial line 102and/or the venous line 104, hematocrit (Hct) and other blood properties,and/or for detecting gaseous bubbles (e.g., air bubbles) in the bloodwithin the arterial line 102 and/or the venous line 104. In someembodiments, the flow rate detection and/or the bubble detection areperformed using sensors such as ultrasonic sensors, optical sensors, orother suitable types of sensors. In other embodiments, sensors fordetecting gaseous bubbles can be located at or in an end cap of thedisposable of the dialyzer 100.

The treatment module 220 also includes an arterial line clamp 242 and avenous line clamp 244. The clamps 242 and 244 are used to either fullyrestrict or fully un-restrict (e.g., in an on/off valve fashion) theflow of blood within the arterial line 102 and/or the venous line 104,respectively.

The treatment module 220 also includes devices for interfacing with thedialyzer 100 to measure pressure at particular locations within thedialyzer 100, as described further below. Additionally, as describedfurther below, the treatment module 220 includes conduits that canselectively interface with the dialyzer 100 to facilitate flow ofliquids such as substituate and/or dialysate between the dialyzer 100and the treatment module 220.

FIGS. 4-7 are schematic diagrams of the dialyzer 100. For ease ofunderstanding, FIG. 4 depicts exclusively the flow of blood through thedialyzer 100; FIG. 5 depicts the flow of blood and substituate; FIG. 6depicts exclusively the flow of dialysate; and FIG. 7 depicts the flowof blood, substituate, and dialysate.

FIGS. 4-7 are simplified to show general flow relationships in thedialyzer 100. For example, the first potting 115 and the second potting116, which secure the two respective ends of each of the fibers of thebundle of hollow fibers 114, are omitted to simplify the illustration.In addition to securing the bundle of hollow fibers, these pottings 115and 116, maintain a barrier between the blood and the dialysate. Thepottings 115 and 116 and the associated flow routing are described infurther detail below in connection with FIGS. 8 to 29 .

Referring to FIG. 4 , the housing 110 of the dialyzer 100 includes thefirst end cap 120, the second end cap 140, and a middle housing portion112 that extends between the first end cap 120 and the second end cap140. The middle housing portion 112 contains the majority of the lengthof the bundle of hollow fibers 114. As indicated above, a more-detaileddescription of the construction of the dialyzer 100, including thebundle of hollow fibers 114 is provided below in connection with thedescription of FIGS. 8 to 29 .

The first end cap 120 includes a pump housing 130. A rotatablecentrifugal pump rotor 132 is located within the pump housing 130. Thepump rotor 132 is enclosed or encased within the pump housing 130.Accordingly, the pump rotor 132 is contained at a fixed positionrelative to the bundle of hollow fibers 114.

In accordance with some embodiments, the pump rotor 132 is a radiallypumping pump wheel with a hollow central volume. The blades (or vanes)of the pump wheel of the pump rotor 132 are arranged so that theyproject or extend at least partially radially. In some cases, the bladesare arranged to project or extend entirely radially. In some cases, theblades are arranged to project or extend partially radially andpartially tangentially.

As described further herein, the pump rotor 132 is operated andcontrolled by interfacing with the pump drive unit 230 (shown in FIGS. 2and 3 ) of the treatment module 220. That is, the pump rotor 132 can belevitated and rotated by magnetic fields that are caused to emanate fromthe pump drive unit 230 during use.

The housing 110 defines one or more pressure detection chambers. Thedepicted embodiment includes an arterial pressure detection chamber 122and a venous pressure detection chamber 142. The arterial pressuredetection chamber 122 is located prior to the pump rotor 132. That is,the arterial pressure detection chamber 122 is arranged to facilitatemeasuring pre-pump arterial pressure. Additionally or alternatively, insome embodiments, pressure can be measured post-pump (but prior to thehollow fibers 114). As described further below, the pressure detectionchambers 122 and 142 are each configured to interface with a respectivepressure transducer of the treatment module 220.

The flow path of blood through the dialyzer 100 will now be explained inreference to the dashed lines shown in FIG. 4 . Blood flows into thefirst end cap 120 via the arterial line 102 (shown in FIGS. 2 and 3 ).The fluid flow path entering the first end cap 120 is transverse to alongitudinal axis of the dialyzer 100. The arterial pressure detectionchamber 122 is located along the flow path after entering the first endcap 120 but prior to the pump rotor 132. The blood flow path transitionsto parallel to the longitudinal axis of the dialyzer 100 to deliver theblood to the pump rotor 132. The blood is directed to a center of thepump rotor 132. Rotations of the centrifugal pump rotor 132 force theblood radially outward from the pump rotor 132. Then, after flowingradially outward from the pump rotor 132, the blood turns and flowslongitudinally toward the middle housing portion 112. The blood entersthe lumens of the bundle of hollow fibers 114 and continues flowinglongitudinally toward the second end cap 140. After passing through themiddle housing portion 112, the blood exits the bundle of hollow fibers114, enters the second end cap 140, and flows transversely out of thesecond end cap 140 via the venous line 104. The venous pressuredetection chamber 142 is located along the blood flow path in the secondend cap 140. In some embodiments, a one-way check valve is located alongthe blood flow path as the blood exits the second end cap 140 into thevenous line 104. In some embodiments, a one-way check valve is includedon side-arm connections to the blood flow pathway to prevent back-fluidflow or blood entering the side arm connection.

The second end cap 140 can also be configured to deaerate the blood asit enters and flows through the second end cap 140. Accordingly, thesecond end cap 140 includes an air purge member 144 that allows air andother gases to exit the second end cap 140 while preventing fluids suchas blood from exiting therethrough. The air purge member 144 can also beused as an access port. That is, the air purge member 144 can beconfigured for uses such as sample extraction and administration ofmedicaments (e.g., heparin). The air purge member 144 can comprise aplastic tube extending from the second end cap 140. An elastomeric sealmember located within the plastic tube is configured to open when asyringe without a needle is coupled with the air purge member 144.

Again, blood passing through the dialyzer 100 for its purification andtreatment flows through the lumens of the hollow fibers 114 (whiledialysate flows through the dialyzer 100 over/along the outsides of thehollow fibers 114 in the spaces between the outsides of the hollowfibers 114, as described further herein). This is in direct contrast tohow blood flows through extracorporeal blood oxygenator devices (whichalso use hollow fibers made of a permeable material). Extracorporealblood oxygenators are used to perform treatments such as extracorporealmembrane oxygenation (“ECMO”) and, in conjunction with a heart-lungmachine, for surgical procedures such as coronary artery bypass grafting(“CABG”), heart valve replacement/repair, heart transplant, and thelike. While extracorporeal blood oxygenators, like the dialyzer 100, caninclude a bundle of hollow fibers made of a permeable material, bloodpassing through the extracorporeal blood oxygenators flows over/alongthe outsides of the hollow fibers (as opposed to through the lumens ofthe hollow fibers as is the case for the dialyzer 100), and gases flowthrough the lumens of the hollow fibers.

Accordingly, because of the fundamentally differing types of blood flowpaths of the dialyzer 100 in comparison to an extracorporeal bloodoxygenator, there is a significant difference between the pressure andflow parameters of blood passing through the dialyzer 100 in comparisonto blood passing through an extracorporeal blood oxygenator. Table 1below shows some blood pressure and flow parameters for Dialysis (usinga dialyzer) and for Extracorporeal Oxygenation (using an extracorporealblood oxygenator).

TABLE 1 Parameter Dialysis Extracorporeal Oxygenation Flow Rate 300mL/min (typical) 1000 to 5000 mL/min (typical) 650 mL/min (maximum)10000 mL/min (maximum) Pressure 500 mmHg (667 mbar) to 1500 500 mmHg(667 mbar) (typical) mmHg (2000 mbar) (typical) Example Pressure 700mmHg (933 mbar) at 250 mmHg (333 mbar) at at Flow Rate 300 mL/min 1000mL/min Example Ratio of 933 mbar/300 mL/min = 3.11 333 mbar/1000 mL/min= 0.33 Pressure to Flow Rate (“Hemolysis Risk Factor”)

The ratio of the pressure to the flow rate that is associated with bloodflowing through a dialyzer or an extracorporeal oxygenator can also betermed as the “hemolysis risk factor.” The risk of causing hemolysis(damage to red blood cells) tends to increase as the pressure to flowrate ratio is increased. Accordingly, the term “hemolysis risk factor”quantifies a useful parameter associated with the physical constructionand usage of dialyzer and extracorporeal oxygenator devices.

From Table 1, it can be observed that blood experiences a much higherhemolysis risk factor (the ratio of pressure to flow rate during usage)using the dialyzer 100, for example, than during extracorporealoxygenation. For example, in the example of Table 1, the hemolysis riskfactor is 3.11 for dialysis and 0.33 for extracorporeal oxygenation.That is approximately a 10 to 1 difference. In other words, the ratio ofpressure to flow rate, or the hemolysis risk factor, is approximately 10times greater during dialysis than during extracorporeal oxygenation.This comparison is one way to illustrate and understand the substantialphysical differences between dialyzers (such as the dialyzer 100, forexample) and extracorporeal oxygenator devices.

Referring to FIG. 5 , the dialyzer 100 is also configured to receive oneor more additions of substituate fluid that are combined with the bloodwithin the dialyzer 100. For example, in the depicted embodiment, thefirst end cap 120 defines a first substituate liquid port 124 and thesecond end cap 140 defines a second substituate liquid port 148. Thefirst substituate liquid port 124 is in direct fluid communication withthe incoming blood flow path defined by the first end cap 120, and isconfluent therewith prior to the arterial pressure detection chamber122. Alternatively, in some embodiments substituate fluid can be addedto the blood after exiting the pump housing 130 (i.e., after beingpressurized by the pump rotor 132) but prior to entering the lumens ofthe hollow fibers 114. The second substituate liquid port 148 is indirect fluid communication with the outgoing blood flow path defined bythe second end cap 140, and is confluent therewith after the venouspressure detection chamber 142. Each of the substituate liquid ports 124and 148 can include a respective one-way check valve therein thatprevents liquid from exiting the end caps 120 and 140 via thesubstituate liquid ports 124 and 148.

Referring to FIG. 6 , the dialyzer 100 is also configured to receivedialysate, and to direct the dialysate to flow through the housing 110.For example, in the depicted embodiment, the second end cap 140 definesa dialysate inlet port 149 and the first end cap 120 defines a dialysateoutlet port 125. The dialysate flows into the second end cap 140 via thedialysate inlet port 149, and then enters the middle housing portion 112containing the bundle of hollow fibers 114. The dialysate flows throughthe middle housing portion 112 via the spaces defined between the outerdiameters of the fibers of the bundle of hollow fibers 114. In otherwords, while the blood flows within the lumens of the fibers of thebundle of hollow fibers 114, the dialysate liquid flows along theoutsides of the fibers. The semi-permeable walls of the fibers of thebundle of hollow fibers 114 separate the dialysate liquid from theblood. The dialysate liquid flows out of the middle housing portion 112and into the first end cap 120. The dialysate liquid exits the first endcap 120 via the dialysate outlet port 125.

Referring to FIG. 7 , the flow paths of blood, substituate, anddialysate (as each are described in reference to FIGS. 4-6 above) arenow shown in combination (e.g., as would occur during use of thedialyzer 100). When substituate is added, the substituate is combineddirectly with the blood in the end cap(s) 120 and/or 140. In contrast,the dialyzer 100 keeps the dialysate separated from the blood. However,waste products from the blood (e.g., urea, creatinine, potassium, andextra fluid) are transferred by osmosis from the blood to the dialysatethrough the semi-permeable walls of the fibers of the bundle of hollowfibers 114 in the dialyzer 100.

Referring to FIGS. 8-10 , the description of the structure and functionof the dialyzer 100 provided above in the context of the schematicdiagrams of FIGS. 4-7 can be used to promote an understanding of thestructure and function of the actual embodiment of the dialyzer 100shown here. The dialyzer 100 includes the housing 110 comprising thefirst end cap 120, the middle housing portion 112 containing the bundleof hollow fibers 114, and the second end cap 140. The arterial line 102is connected to the first end cap 120. The venous line 104 is connectedto the second end cap 140. In this example, the arterial line 102 andthe venous line 104 are permanently bonded (e.g., solvent bonded, laserwelded, etc.) to the first end cap 120 and the second end cap 140,respectively. It should be understood, however, that in other examples,one or both of these connections may utilize any other suitablepermanent or removable fluid-tight connection, including, for example,press fits and latchable connectors.

The first end cap 120 includes the pump housing 130, the firstsubstituate liquid port 124, and the dialysate outlet port 125. Thefirst end cap 120 also includes the arterial pressure detection chamber122. The exterior wall of the arterial pressure detection chamber 122(as visible in the rear view of FIG. 8 ) comprises a flexible membrane160. As described further herein (e.g., in reference to FIGS. 31-33 ), apressure transducer of the treatment module 220 (e.g., FIGS. 1-3 and 30) interfaces with (e.g., abuts against) the flexible membrane 160 of thearterial pressure detection chamber 122 while the dialyzer 100 isoperational with the treatment module 220.

The second end cap 140 includes the second substituate liquid port 148,the dialysate inlet port 149, and venous pressure detection chamber 142.The exterior wall of the venous pressure detection chamber 142 (asvisible in the rear view of FIG. 8 ) comprises a flexible membrane 162.As described further herein (e.g., in reference to FIGS. 31-33 ), apressure transducer of the treatment module 220 (e.g., FIGS. 1-3 and 30) interfaces with (e.g., abuts against) the flexible membrane 162 of thevenous pressure detection chamber 142 while the dialyzer 100 isoperational with the treatment module 220. The air purge member 144 isalso attached to the second end cap 140 and is in fluid communicationwith the interior of the second end cap 140.

Referring to FIGS. 20-22 , here the first end cap 120 is shown inisolation from other portions of the dialyzer 100 so that structuraldetails of the first end cap 120 are visible in greater detail. In FIGS.21 and 22 , the arterial flexible membrane 160 is not shown in order tofacilitate illustration of other features of the arterial pressuredetection chamber 122. Referring also to the cross-sectional view ofFIG. 16 , blood to be treated in the dialyzer 100 flows into the firstend cap 120 via the arterial line 102. The blood enters an arterialmixing chamber 163, from which the blood then flows into the arterialpressure detection chamber 122. The blood can either pass through thearterial mixing chamber 122 undiluted or be mixed with substituatefluid, such as, for example, when the blood treatment system 1 isoperating in a pre-dilution HDF mode.

In situations (e.g., pre-dilution HDF) where substituate is added to thearterial mixing chamber, the substituate flows into the first end cap120 from a first substituate supply conduit 254 via the firstsubstituate liquid port 124. The substituate then flows through anarterial substituate supply tube 165. The substituate then passesthrough a check valve 167 and into the arterial mixing chamber 163. Thisflow of substituate is illustrated via the series of arrows in FIG. 16extending from the first substituate liquid inlet port 124 to the outletof the check valve 167. In the arterial mixing chamber 163, thesubstituate mixes with the incoming arterial blood flow (illustrated byan upwardly pointing arrow) before passing through an arterial pressuredetection chamber inlet 122 i. The check valve 167 prevents the flow ofblood into the arterial substituate supply tube 165 and the firstsubstituate liquid inlet port 124. This prevents blood contamination ofthe first substituate supply conduit 254.

The blood (either undiluted or diluted with substituate, depending onthe mode of operation of the treatment system 1) flows through thearterial pressure detection chamber inlet 122 i and into the arterialpressure detection chamber 122. The flow of the blood through thearterial pressure detection chamber 122 allows an arterial pressuretransducer 250 (illustrated in FIGS. 31-33 ) of the blood treatmentmodule 200 to measure the arterial blood pressure via membrane 160. Theblood exits the arterial pressure detection chamber 122 via an arterialpressure detection chamber outlet 122 o, as illustrated by the arrows inFIG. 13 . After exiting the arterial pressure detection chamber 122, theblood then flows through a rotor supply tube 103 toward the pump housing130. The rotor supply tube 103 defines a fluid flow path that istransverse to the longitudinal axis Z of the dialyzer 100.

The first end cap 120 also includes the dialysate outlet port 125. Thedialysate flows from a peripheral inner wall area of the first end cap120 through a dialysate outlet tube 126 to the dialysate outlet port125. As illustrated in FIG. 16 , a one-way flow valve 16 (e.g., checkvalve) can be included in the first substituate liquid port 124 and thearterial line 102.

Referring to FIGS. 13 and 23 , the flow path of the blood (which, asindicated above, may be undiluted or diluted with substituate) throughthe first end cap 120 can be visualized to a greater extent in thelongitudinal cross sectional view of the dialyzer 100 of FIG. 13 and thepartial longitudinal cross-sectional perspective view of the first endcap 120 in FIG. 23 . The blood flows toward the pump housing 130 throughthe rotor supply tube 103. A 90° elbow at the end of the rotor supplytube 103 directs the blood to turn and flow parallel along thelongitudinal central axis Z of the dialyzer 100 at the center of thefirst end cap 120. From the exit of the rotor supply tube 103, the bloodis delivered to a center of a pump rotor 132 located within the pumphousing 130.

Referring also to FIG. 24 , the example pump rotor 132 includes a firstplate 133, a magnetic disc 136, and a plurality of vanes 135 (or blades)extending between the first plate 133 and the magnetic disc 136. Inaccordance with some embodiments, the pump rotor 132 is a pump impellercomprising a radially pumping pump wheel with a hollow central volume.Accordingly, the depicted pump rotor 132 can also be referred to a pumpimpeller. The blades (or vanes) of the pump wheel of the pump rotor 132can be arranged so that they project or extend at least partiallyradially. In some cases, the blades are arranged to project or extendentirely radially. In some cases, the blades are arranged to project orextend partially radially and partially tangentially.

The first plate 133 is an annular ring that defines a central aperture134. In some embodiments, the first plate 133 is omitted and the vanes135 extend from the magnetic disc 136 and terminate without the firstplate 133. The magnetic disc 136 defines a central lumen 131 (FIG. 23 )that extends along the longitudinal central axis Z of the dialyzer 100.The magnetic disc 136 can include an un-encapsulated or an encapsulatedbi-pole magnet (e.g., a rare earth magnet, a ferrite ceramic magnet, andother suitable types of magnets). In the depicted embodiment, the vanes135 are arcuate members.

Rotation of the pump rotor 132 causes blood to flow as depicted by thelarge arrows of FIGS. 13 and 23 . In some embodiments, the pump rotor132 is driven during operation to rotate at a speed (revolutions perminute) in a range of 5,000 rpm to 25,000 rpm, or 5,000 rpm to 22,000rpm, or 7,000 rpm to 20,000 rpm, or 9,000 rpm to 18,000 rpm, or 11,000rpm to 16,000 rpm, or 12,000 rpm to 15,000 rpm, or 13,000 rpm to 14,000rpm, without limitation.

In some embodiments, the height of the vanes 135 (measured along thelongitudinal central axis Z) is in a range of 2 mm to 10 mm, or 2 mm to8 mm, or 2 mm to 6 mm, or 3 mm to 5 mm, or 3 mm to 4 mm, withoutlimitation.

In some embodiments, the diameter of the exit of the rotor supply tube103 is in a range of 5 mm to 10 mm, or 6 mm to 9 mm, or 7 mm to 8 mm,without limitation. In some embodiments, the diameter of the centralaperture 134 of the pump rotor 132 is in a range of 4 mm to 12 mm, or 5mm to 11 mm, or 6 mm to 10 mm, or 7 mm to 9 mm. In some embodiments, thediameter of the central lumen 131 is in a range of 2 mm to 10 mm, or 3mm to 9 mm, or 4 mm to 8 mm, or 5 mm to 7 mm, without limitation.Accordingly, in some embodiments the diameter of the central aperture134 of the pump rotor 132 is larger than, equal to, or smaller than thediameter of the exit of the rotor supply tube 103. Further, in someembodiments the diameter of the central lumen 131 of the pump rotor 132is larger than, equal to, or smaller than the diameter of the exit ofthe rotor supply tube 103. Moreover, in some embodiments the diameter ofthe central aperture 134 of the pump rotor 132 is larger than, equal to,or smaller than the diameter of the exit of the rotor supply tube 103.

In some embodiments, during operation (e.g., while the pump rotor 132 islevitating) the clearance space between the top surface of the firstplate 133 and the opposing lower surface of the internal support plate121 is in a range of 1 mm to 3 mm, or 2 mm to 3 mm, or 1.5 mm to 2.5 mm,or 1 mm to 5 mm, without limitation. Similarly, in some embodiments,during operation (e.g., while the pump rotor 132 is levitating) 0 theclearance space between the bottom of the magnetic disc 136 and theopposing surface of the pump housing 130 is in a range of 1 mm to 3 mm,or 2 mm to 3 mm, or 1.5 mm to 2.5 mm, or 1 mm to 5 mm, withoutlimitation. In some embodiments, during operation the ratio of theclearance spaces between: (i) the top surface of the first plate 133 andthe opposing lower surface of the internal support plate 121, incomparison to (ii) the bottom of the magnetic disc 136 and the opposingsurface of the pump housing 130 is in a range of 1.1:1.0 to 1.2:1.0, or0.8:1.0 to 1.0:1.0, or 1.0:1.0 to 1.3:1.0, or 0.9:1.0 to 1.1:1.0,without limitation.

In some embodiments, the outer diameter of the magnetic disc 136 is in arange of 15 mm to 25 mm, or 17 mm to 22 mm, or 18 mm to 20 mm, withoutlimitation. In some embodiments, the inner diameter of the cylindricalinner wall of the pump housing 130 is in a range of 15 mm to 25 mm, or17 mm to 23 mm, or 18 mm to 22 mm, or 19 mm to 21 mm, withoutlimitation. Accordingly, in some embodiments the radially clearancespace between the cylindrical outer wall of the pump rotor 132 and thecylindrical inner wall of the pump housing 130 is in a range of 0.3 mmto 1.1 mm, or 0.4 mm to 0.9 mm, or 0.5 mm to 0.8 mm, or 0.6 mm to 0.7mm, without limitation.

The blood flows toward the pump rotor 132, passes through the centralaperture 134, and is forced radially outward from the pump rotor 132 bythe rotation of the vanes 135. Referring again to FIGS. 13 and 23 , asthe blood flows generally radially away from the pump rotor 132, theblood enters a toroidal space 128 defined by the pump housing 130 and/orthe arterial end cap 120. Within the toroidal space 128, the blood isforced by the inner wall of the pump housing 130 to turn and flowparallel to the longitudinal axis Z of the dialyzer 100 toward thehollow fiber bundle 114.

In some embodiments, the diameter of the toroidal space 128 is largerthan the diameter of the cylindrical inner wall of the pump housing 130(which contains the magnetic disc 136) by a range of 10 mm to 17 mm, or11 mm to 16 mm, or 12 mm to 15 mm, or 13 mm to 15 mm, or 14 mm to 15 mm,without limitation.

The first end cap 120 includes an internal support plate 121. The rotorsupply tube 103 can be attached to and/or supported by the internalsupport plate 121. The internal support plate 121 is also attached tocircumferential portions of an inner wall of the first end cap 120,while defining multiple openings (e.g., slots, circular openings, etc.)123 therebetween. The openings/slots 123 provide passages for the bloodto flow from the pump housing 130 toward the hollow fiber bundle. In thedepicted embodiment, there are four arcuate slots 123 through which theblood can flow. In some embodiments, there is a single opening/slot 123,or two openings/slots 123, three openings/slots 123, four openings/slots123, five openings/slots 123, six openings/slots 123, sevenopenings/slots 123, eight openings/slots 123, or more than eightopenings/slots 123.

Due to the increased pressure created by the rotating pump rotor 132,the blood is pushed through the interior spaces (or lumens) of each ofthe hollow fibers of the bundle of hollow fibers 114. The blood entersthe fibers via openings exposed on the surface of potting 115. Since thepotting 115 is sealed against the arterial end cap 120, the pressurizedblood is forced through the lumens of the hollow fibers of the bundle ofhollow fibers 114, which pass through and are supported by the potting115. In this example, the potting 115 is sealed against the arterial endcap 120 by a gasket 170, which is axially (i.e., in the direction oflongitudinal axis Z) compressed between the outer periphery of thepotting 115 and the interior wall of the arterial end cap 120. A secondgasket 171 performs an analogous function with respect to the venous endcap 140 and potting 116.

As the blood flows axially through the lumens of the bundle of hollowfibers 114, dialysis takes place across the semipermeable fibermembranes with the dialysate flowing (in a counterflow direction) in thespace surrounding the fibers 114. The blood then flows, still within thehollow fibers 114, through a second potting 116 in the venous end cap140, and into an interior space 146 in the upper dome 145 of the venousend cap 140.

Again, while the dialyzer 100 is being used, dialysate flows from thevenous end cap 140 to the arterial end cap 120 along the outer surfacesof the hollow fibers 114 such as within the spaces defined between thehollow fibers 114. If flow rate measurements of the dialysate were takenat various points along a radius of a cross-section transverse to thelongitudinal axis Z, the measurements would show that in many cases theaxial flow rate of the dialysate is not entirely uniform within thehollow fibers 114. That is, in many cases it would be seen that the flowrate of the dialysate is higher near the outer areas of the bundle ofhollow fibers 114 than at the inner areas of the bundle of hollow fibers114. In other words, there is a tendency for more dialysate to flowthrough the dialyzer 100 along the outer annular portions of the bundleof hollow fibers 114 than through the central portion of the bundle ofhollow fibers 114.

The arterial end cap 120 is advantageously designed to direct blood toflow through the bundle of hollow fibers 114 in a manner that enhancesdialysis efficiency in view of the non-uniform flow rate of thedialysate as described above. For example, the arterial end cap 120includes the arcuate slots 123 through which blood is directed to flowin route to entering the bundle of hollow fibers 114. The radiallocations of the arcuate slots 123 are biased toward outer annularportions of the bundle of hollow fibers 114 (as compared to the centralportion of the bundle of hollow fibers 114). Accordingly, the arterialend cap 120 causes blood to flow through the outer annular portions ofthe bundle of hollow fibers 114 at a higher rate than the centralportion of the bundle of hollow fibers 114 in a manner thatadvantageously matches the higher flow regions of the dialysate. Thismatching of the flow rate profiles of the blood and the dialysate isconducive to enhancing dialysis efficiency, as compared to havingdisparate flow rate profiles of the blood and dialysate.

The arterial end cap 120 is also advantageously designed to reduce thepotential for blood hemolysis (damage to red blood cells). As describedabove, blood exiting the rotor 132 flows generally radially from thevanes 135 into the toroidal space 128. However, by virtue of therotation of the rotor 132, the blood within the toroidal space 128 alsohas a tendency to flow substantially circularly (e.g., like a vortex).If the blood was forced to flow into the lumens of the hollow fibers 114while still flowing in such a substantially circular manner, theresulting dynamic shear stresses would tend to cause hemolysis.Fortunately, the internal support plate 121 of the arterial end cap 120is designed to reduce the circular flow of the blood, and thereby reducethe potential for hemolysis. For example, the arcuate slots 123, throughwhich blood is directed to flow in route to entering the bundle ofhollow fibers 114, reduce the circular flow of the blood. Instead, thearcuate slots 123 cause the blood to flow more axially toward theentries to the lumens of the hollow fibers 114. Accordingly, by reducingthe circular flow of the blood as it enters the lumens of the hollowfibers 114, the arcuate slots 123 of the internal support plate 121reduce the potential for dynamic shear stresses of the blood, and reducethe potential for hemolysis.

As described above, the pump rotor 132 defines the central lumen 131.The central lumen 131 extends through the pump rotor 132 from the areaof the vanes 135 and all the way through the magnetic disc 136. In otherwords, the central lumen 131 provides for fluid communication betweenthe area of the vanes 135 and the clearance spaces that exist betweenthe cylindrical outer wall of the pump rotor 132 and the cylindricalinner wall of the pump housing 130. By virtue of the fluid communicationprovided by the central lumen 131, the potential for blood to becomestagnant in areas within the pump housing 130 is mitigated. That is, thecentral lumen 131 helps to keep the blood that is in the clearancespaces between the cylindrical outer wall of the pump rotor 132 and thecylindrical inner wall of the pump housing 130 moving and flowing outtherefrom. Accordingly, the potential for thrombosis in the pump housing130 is reduced as a result of the central lumen 131 of the pump rotor132.

Referring also to FIG. 25 , an alternative pump rotor 137 includes afirst plate 138, a magnetic disc 143, and a plurality of vanes 139radially extending between the first plate 138 and the magnetic disc143. The first plate 138 is annular and defines a central aperture 141.The magnetic disc 143 can include an un-encapsulated or an encapsulatedbi-pole magnet (e.g., a rare earth magnet, a ferrite ceramic magnet, andother suitable types of magnets). In the depicted embodiment, the vanes139 are linear members.

In accordance with some embodiments, the pump rotor 137 is a pumpimpeller comprising a radially pumping pump wheel with a hollow centralvolume. Accordingly, the depicted pump rotor 137 can also be referred toa pump impeller. The blades (or vanes) of the pump wheel of the pumprotor 137 can be arranged so that they project or extend at leastpartially radially. In some cases, the blades are arranged to project orextend entirely radially. In some cases, the blades are arranged toproject or extend partially radially and partially tangentially.

The blood flows toward the pump rotor 137, passes through the centralaperture 141, and is then forced radially outward from the pump rotor137 by the rotation of the vanes 139. As the blood flows radially awayfrom the pump rotor 137, the blood is forced by the inner wall of thepump housing 130 to turn and flow parallel to the longitudinal axis ofthe dialyzer 100 (toward the hollow fiber bundle). The blood then passesthrough the slots 123 defined between the internal support plate 121 andthe inner wall of the first end cap 120. The slots 123 provide passagesfor the blood to flow from the pump housing 130 toward the hollow fiberbundle.

Referring to FIGS. 27-29 , here the venous end cap 140 (or “second endcap 140”) is shown in isolation from other portions of the dialyzer 100so that structural details of the second end cap 140 are visible ingreater detail.

As shown, for example, in FIGS. 13 and 14 , blood that has passedthrough the fiber bundle 114 in the dialyzer 100 and into the second endcap 140 exits the upper dome 145 via a blood exit tube 105.

The second end cap 140 also includes the air purge member 144. The airpurge member 144 can be located at the apex of the upper dome 145. Theair purge member 144 can serve multiple purposes, such as for purgingair (venting) and as an access port (e.g., for sample extraction oradministering medicaments). FIG. 29 shows a cross-sectional view ofanother example venous end cap 340 that differs from end cap 140 in thatincludes an access port 380 (in this case, a needleless access port) inaddition to the air purge member 344. The access port 380 may be used toadminister medicaments or extract samples.

From the blood exit tube 105, the blood enters the venous pressuredetection chamber 142 (having its exterior flexible membranous wall 162)via a venous pressure detection chamber inlet 142 i. The blood exits thevenous pressure detection chamber 142 via a venous pressure detectionchamber outlet 142 o. The flow of the blood through the venous pressuredetection chamber 142 allows a venous pressure transducer 252(illustrated in FIG. 31 ) of the blood treatment module 200 to measurethe venous blood pressure via membrane 162.

After exiting the venous pressure detection chamber 142, the blood thenflows into a venous mixing chamber 164. The blood can either passthrough the venous mixing chamber 142 without post-dilution or be mixedwith substituate fluid, such as, for example, when the blood treatmentsystem 1 is operating in a post-dilution HDF mode.

In situations (e.g., post-dilution HDF) where substitute is added to thevenous mixing chamber, the substituate flows into the second end cap 140from a second substituate supply conduit 256 (illustrated in FIG. 31 )via the second substituate liquid inlet port 148. The substituate flowsthrough a venous substituate supply tube 166. The substituate thenpasses through a check valve 168 and into the venous mixing chamber 164.This flow of substituate is illustrated via the series of arrows in FIG.15 extending from the second substituate liquid inlet port 148 to theoutlet of the check valve 168. In the venous mixing chamber 164, thesubstituate mixes with the incoming venous blood flow from the venouspressure detection chamber 142. The check valve 168 prevents the flow ofblood into the venous substituate supply tube 166 and the secondsubstituate liquid inlet port 148. This prevents blood contamination ofthe second substituate supply conduit 256.

The blood (whether or not post-diluted) exits the venous mixing chamber164 into the venous blood line 104 which conveys the dialyzed blood backto the patient.

The second end cap 140 also includes the dialysate inlet port 149. Thedialysate flows from the dialysate inlet port 149 through a dialysatesupply tube 150 to a peripheral inner wall area of the second end cap140.

The flow path of the dialysate from the dialysate supply conduit 257 tothe dialysate outlet conduit (or spent dialysate conduit) 255 isillustrated in FIGS. 17 to 19 . The blood treatment module 200 isactuated to a) fluid-tightly engage the dialysate supply conduit 257(illustrated in FIG. 31 ) with the dialysate inlet port 149 and b)fluid-tightly engage the spent dialysate conduit 255 with the spentdialysate outlet port 125. The flow of dialysate then begins with thedialysate flowing through the dialysate supply tube 150 into the spacebetween the venous end cap 140 and the potting 116. The dialysate flowsfrom this space axially beyond the potting 116 and radially inwardlythrough openings 118 between axially extending fingers 174 of the middlehousing portion 112. The ends of the fingers 174 are embedded in andsupport the potting 116. The dialysate path is sealed from the bloodvolume in the venous end cap 140 by the gasket 171.

The dialysate's radial inflow via the openings 118 (with the fingers 174helping to distribute the dialysate flow) causes the dialysate to bedistributed circumferentially in a ring-like manner as it flows radiallyinto the spaces between the hollow fibers 114. This peripherallyconcentrated dialysate flow aligns with, or coincides with, the flow ofthe blood through the lumens of the hollow fibers 114 in that the bloodenters the hollow fibers 114 through the peripherally-locatedopenings/slots 123 of the first end cap 120. Accordingly, the design ofthe dialyzer 100 causes the highest flow concentrations of the dialysateand the blood in the region of the hollow fibers 114 to be matched witheach other. This matching of blood and dialysate flow concentrationsenhances the blood treatment efficiency of the dialyzer 100.

After passing through the openings 118, the dialysate flows between thehollow fibers 114 and continues to flow axially downwardly untilreaching the arterial end cap 120. Since potting 115 blocks furtheraxial flow between the fibers 114, the dialysate flows radiallyoutwardly through openings 117 between fingers 173 of the middle housingportion 112, which are embedded in and support the potting 115. Thedialysate path is sealed from the blood volume in the arterial end cap120 by the gasket 170. The dialysate then flows into the space betweenthe arterial end cap 120 and the potting 115. The dialysate then entersthe spent dialysate outlet tube 126 via a spent dialysate tube inlet127. Spent dialysate tube 126 then conveys the dialysate to thedialysate outlet port, where it flows into the spent dialysate conduit255 (illustrated in FIGS. 31-33 ) of the blood treatment module 220.

Referring to FIGS. 30 and 31 , the treatment module 220 defines thefirst complementarily shaped slot 222 and the second complementarilyshaped slot 224 that configure the treatment module 220 to be slidablycoupleable with the first projection 106 and the second projection 108of the dialyzer 100 (e.g., FIGS. 2, 10, and 17 ). The treatment module220 also includes the arterial line clamp 242 and the venous line clamp244. The clamps 242 and 244 are used to either fully restrict or fullyun-restrict the flow of blood within the arterial line 102 and/or thevenous line 104 (e.g., in an on/off valve fashion), or to modulate theflow of blood through the arterial line 102 and/or the venous line 104(e.g., across a range of partially restricting clamp settings).

The treatment module 220 also includes the tubing interface module 240configured to releasably receive a portion of the arterial line 102and/or a portion of the venous line 104. The tubing interface module 240can include devices to perform functions such as flow rate detection,gaseous bubble detection, and the like. That is, the tubing interfacemodule 240 can include sensors for detecting, for example, a flow rateof the blood within the arterial line 102 and/or the venous line 104,and/or for detecting gaseous bubbles (e.g., air bubbles) in the bloodwithin the arterial line 102 and/or the venous line 104. The flow ratedetection and/or the bubble detection can be performed using sensorssuch as ultrasonic sensors, optical sensors, or other suitable types ofsensors.

The treatment module 220 also includes the pump drive unit 230. The pumpdrive unit 230 is configured to releasably receive the pump housing 130of the dialyzer 100 (shown in FIGS. 8, 9, 13, and 15 ) when the dialyzer100 is coupled to the treatment module 220. During operation of thetreatment module 220, one or more electrical coils within the pump driveunit 230 are dynamically energized by the control system of the bloodtreatment machine console 210 (shown in FIG. 1 ). The energization ofthe one or more electrical coils generates dynamic magnetic fields(magnetic fields that move or modulate) that cause the magnetic pumprotor (e.g., rotor 132 or rotor 137) to levitate out of contact with thewalls of the pump housing 130 and to rotate at a desired rotationalspeed. Alternatively, in some embodiments, a mechanical coupling can beused to couple a pump drive unit to a pump rotor within a dialyzer.

The pump drive unit 230 in conjunction with the control system of theblood treatment machine console 210 (shown in FIG. 1 ) can also be usedfor monitoring various conditions of the dialyzer 100. For example, itcan be detected whether the pump housing 130 of the dialyzer 100 is inthe operative position relative to the pump drive unit 230.Additionally, the presence of air in the pump housing 130 can bedetected. If air is detected within the pump housing 130, substituatecan be added via the first substituate liquid port 124 to prime themagnetic pump rotor. Occlusions within the dialyzer 100 can also bedetected by the pump drive unit 230 in conjunction with its controlsystem.

The treatment module 220 also includes pressure measurement devices thatinterface with the dialyzer 100 to measure pressures in the arterialpressure detection chamber 122 and the venous pressure detection chamber142 (shown in FIGS. 8, 11, 12, 18, and 19 ). Moreover, the treatmentmodule 220 includes conduits for supplying substituate (via thesubstituate liquid ports 124 and 148) to the dialyzer 100 and forconveying dialysate (via the dialysate ports 125 and 149) to and fromthe dialyzer 100. Such pressure measurement devices and conduits can becontrolled by the treatment module 220 to extend to engage with thedialyzer 100, and retract to disengage from the dialyzer 100.

In FIG. 30 , the pressure measurement devices and conduits are retractedand covered by a first door 246 and a second door 248. In FIG. 31 , thedoors 246 and 248 are opened, and the pressure measurement devices andconduits are extended (as they would be in order to interface with thedialyzer 100). When closed, the doors 246 and 248 allow for convenientwiping to clean the outer surfaces of the treatment module 220.Additionally, with the pressure measurement devices and conduitsretracted internally within the treatment module 220 (and the doors 246and 248 closed), the pressure measurement devices and conduits can beautomatically cleaned and prepared for subsequent use while they arewithin the treatment module 220.

In FIG. 31 , the doors 246 and 248 are in their opened positions and thepressure measurement devices and conduits are extended into theiroperative positions (as if a dialyzer 100 was coupled with the treatmentmodule 220). For example, a first pressure transducer 250 is extended tointerface with the flexible membrane wall of the arterial pressuredetection chamber 122 of the dialyzer 100, and a second pressuretransducer 252 is extended to interface with the flexible membrane wallof the venous pressure detection chamber 142 of the dialyzer 100.

Additionally, the treatment module 220 includes two pairs of conduitsthat can automatically interface with the dialyzer 100 to facilitateflow of liquids such as substituate and/or dialysate between thedialyzer 100 and the treatment module 220. For example, a first pair ofconduits (a first substituate supply conduit 254 and a dialysate outletconduit 255) is positioned to respectively couple with the firstsubstituate liquid port 124 and the dialysate outlet port 125 located onthe first end cap 120 of the dialyzer 100. In addition, a second pair ofconduits (a second substituate supply conduit 256 and a dialysate supplyconduit 257) is positioned to respectively couple with the secondsubstituate liquid port 148 and the dialysate inlet port 149 located onthe second end cap 140 of the dialyzer 100. The extension and retractionof the conduits 254-257 and the pressure measurement transducers 250 and252 can be controlled by the control system of the blood treatmentmachine 200 (FIG. 1 ).

Referring to FIGS. 32-34 , isolated views showing greater detail of howthe first end cap 120 interfaces with the first pressure transducer 250,the first substituate supply conduit 254, and the dialysate outletconduit 255 are provided. It should be understood that the relativearrangement of the second end cap 140 in relation to the second pressuretransducer 252, the second substituate supply conduit 256, and thedialysate supply conduit 257 is analogous.

The face of the first pressure transducer 250 (when extended, as shownin FIG. 24 ) abuts against a flexible membrane 122 m that serves as anexterior wall of the arterial pressure detection chamber 122. The firstsubstituate supply conduit 254 (when extended, as shown in FIG. 24 )fluidly couples with the first substituate liquid port 124 in aliquid-tight manner. The dialysate outlet conduit 255 (when extended, asshown in FIG. 24 ) fluidly couples with the dialysate outlet port 125 ina liquid-tight manner.

In order to provide a highly efficacious interface between the flexiblemembrane 122 m and the first pressure transducer 250, the arterialpressure detection chamber 122 is pressurized prior to extending thefirst pressure transducer 250 into contact with the flexible membrane122 m. While the arterial pressure detection chamber 122 is pressurized,the flexible membrane 122 m will bulge outward to present a convexsurface to the first pressure transducer 250. Then, while the flexiblemembrane 122 m is bulged outward, the first pressure transducer 250 isextended to abut against the flexible membrane 122 m so as to seal theinterface therebetween. This technique can help to establish strongcoupling cohesion between the first pressure transducer 250 and theflexible membrane 122 m by reducing the potential for air pocketstherebetween, for example. In some embodiments, negative air pressure(vacuum) can be applied to create or enhance the coupling cohesionbetween the first pressure transducer 250 and the flexible membrane 122m.

FIG. 35 shows another example blood treatment module 1220 and dialyzer1100. This arrangement differs from that of module 220 and dialyzer 100in that the dialysate and substituate ports and the pressure chambersand membranes are instead located in the arterial end cap. Accordingly,the blood treatment module 1220 interfaces only the arterial end cap1120 for supplying fresh dialysate, receiving spent dialysate, supplyingpre- and post-dilution substituate fluid, and monitoring arterial andvenous pressures. In this arrangement, a pair of tubes 1190 are providedto convey the fresh dialysate and the post-dilution substituate from thearterial end cap 1120 to the venous end cap 1140.

FIG. 36 is a perspective view of an alternative first (arterial) end cap520 shown in a partial longitudinal cross-sectional view. The end cap520 can be used with the dialyzer 100 as an alternative to the end cap120, for example.

The incoming blood flows toward the pump housing 530 through the rotorsupply tube 503 that is supported by an internal support plate 521. A90° elbow at the end of the rotor supply tube 503 directs the blood toturn and flow parallel along the longitudinal central axis of thedialyzer 100 at the center of the first end cap 520. From the exit ofthe rotor supply tube 503, the blood is delivered to a center of a pumprotor 532 located within the pump housing 530. The blood radially exitsthe pump rotor 532 into a toroidal space 528 circumferentiallysurrounding the portion of the rotor 532 that includes blades 535. Thetoroidal space 528 is shaped so as to direct the blood axially towardthe bundle of hollow fibers. The toroidal space 528 is partially definedby annular concave wall surface of the housing 530, which is opposite ofthe bundle of hollow fibers. After being redirected from radial flow tolongitudinal flow in the toroidal space 528, then the blood passesthrough one or more openings 523 defined in the internal support plate521 and continues flowing toward the bundle of hollow fibers. In someembodiments, the openings 523 are slots (e.g., linear or arcuate slots).Any number of openings 523, such as one, two, three, four, five, six,seven, eight, or more than eight can be included.

The pump rotor 532 includes first end portion 537 and a second endportion 538 that are on opposite ends of the pump rotor 532. The firstend portion 537 houses, or has attached thereto, one or more magnets,such as a magnetic disc 536. The second end portion 538 comprises afirst plate 533 and a plurality of vanes 535 extending between the firstplate 533 and the magnetic disc 536. The first end portion 537 isdiametrically smaller than the second end portion 538.

In accordance with some embodiments, the pump rotor 532 is a pumpimpeller comprising a radially pumping pump wheel with a hollow centralvolume. Accordingly, the depicted pump rotor 532 can also be referred toa pump impeller. The vanes 535 of the pump wheel (second end portion538) of the pump rotor 532 can be arranged so that they project orextend at least partially radially. In some cases, the blades arearranged to project or extend entirely radially. In some cases, theblades are arranged to project or extend partially radially andpartially tangentially. The first plate 533 is an annular ring thatdefines a central aperture 534. The magnetic disc 536 defines a centrallumen 531 that extends along the longitudinal central axis Z of thedialyzer 100. The magnetic disc 536 can include one or more encapsulatedor non-encapsulated bi-pole magnets (e.g., a rare earth magnet, aferrite ceramic magnet, and other suitable types of magnets). In thedepicted embodiment, the vanes 535 are arcuate members, but the vanes535 can be linear members in some embodiments.

In some embodiments, the components of the end cap 520 can have the samephysical dimensions and dimensional interrelations as described above inreference to the components of the end cap 120. However, the end cap 520differs from the end cap 120 at least in the following aspects. Theouter edges of the vanes 535 are not parallel to the center axis.Instead, an acute angle is defined between the outer edges of the vanes535 and the center axis. In some embodiments, the acute angle is in arange of 0° to 60°, or 0° to 45°, or 5° to 40°, or 10° to 35°, or 20° to35°, or 25° to 35°, or 30° to 45°, without limitation. In addition, insome embodiments the height of the vanes 535 are less than the height ofthe vanes 135. For example, in some embodiments the height of the vanes535 (measured along the longitudinal central axis Z) is in a range of 1mm to 8 mm, or 1 mm to 6 mm, or 1 mm to 5 mm, or 1 mm to 4 mm, or 1 mmto 3 mm, or 2 mm to 3 mm, without limitation. Further, the toroidalspace 528 is shaped differently from the toroidal space 128. Forexample, the inner surface of the housing that defines the lower wall ofthe toroidal space 528 is concave (curved downward), whereas the lowersurface of the toroidal space 128 is planar or curved upward. The shapeof the toroidal space 528 promotes vortexing in the flow that exitsradially from the pump rotor 532 and promotes a transition (redirection)of the flow toward the upward axial direction.

These physical features of the end cap 520, and its pump rotor 532,serve to maximize axial thrust of the blood flow and to stabilize thepump rotor 532 during operation. In essence, pump rotor 532 and thetoroidal space 528 redirect the blood flow by 180° instead of 90°. Insome embodiments, blood is introduced axially in the “top” of the pumprotor 522 and is conveyed to the “bottom” of the rotor 532.

The blood exits the end cap 520 via the one or more openings 523 in acircular pattern that is concentric to the central aperture 534. The oneor more openings 523 can be a symmetrical circular arrangement of holes,or one or more slits in the shape of circular/arcuate segments.Accordingly, no eccentric forces act upon the pump rotor 532 (unlikemost centrifugal pumps having a tangential outlet). As a consequence,the pump rotor 532 is more stable (e.g., with substantially reducedtilting moment) during operation, and the dimensional gaps between itand the surrounding housing surfaces remain within tolerance.Advantageously, because the pump rotor 532 is more stable duringoperation, the strength of the magnetic field required for levitatingand driving the pump rotor 532 is lessened. So, for example, in someembodiments lower cost hard ferrite magnets can be used, therebysubstantially reducing the cost of the pump rotor 532.

The shape of the toroidal space 528 promotes a transition (redirection)of the flow of blood from radial toward the upward axial direction. Thatupward blood flow from the toroidal space 528 is substantiallyconcentrated at the periphery or circumference of the exit from thetoroidal space 528. That concentration of blood flow also advantageouslyaligns with the locations of the openings 523 (which are, in turn, inalignment with outer peripheral portions of the bundles of hollowfibers). Moreover, as described above in reference to FIGS. 17-19 , thedialysate's flow is concentrated in a circumferential ring-like manneras it flows radially into the spaces between the hollow fibers 114. Theperipherally-concentrated dialysate flow aligns with, or coincides with,the peripherally-concentrated flow of the blood through the lumens ofthe hollow fibers 114. Accordingly, the design of the dialyzer 100advantageously causes or aligns the highest flow concentrations of thedialysate and the blood to be matched in the same areas with each other.This matching of blood and dialysate flow concentrations enhances theblood treatment efficiency of the dialyzer 100.

While certain embodiments have been described, other embodiments arepossible, and are within the scope of this disclosure.

While systems capable of HDF are described, some embodiments omitsubstituate ports. Such machines may perform hemodialysis but notinclude HDF capability. For example, a dialyzer 2100 that is configuredlike the dialyzer of the blood treatment system of FIG. 1 , exceptwithout HDF capability is depicted in FIGS. 37-39 . The housing 2110 ofthe dialyzer 2100 includes a first end cap 2120, a second end cap 2140,and a middle housing portion 2112 that extends between the first end cap2120 and the second end cap 2140. The middle housing portion 2112contains the majority of the length of a bundle of hollow fibers 2114.

The first end cap 2120 includes a pump housing 2130. A rotatablecentrifugal pump rotor (not visible) is located within the pump housing2130. As described further herein, the pump rotor is operated andcontrolled by interfacing with the pump drive unit (e.g., as shown inFIGS. 2 and 3 ) of the treatment module 220. That is, the pump rotor canbe levitated and rotated by magnetic fields that are caused to emanatefrom the pump drive unit during use.

The housing 2110 defines one or more pressure detection chambers. Thedepicted embodiment includes an arterial pressure detection chamber 2122and a venous pressure detection chamber 2142. The arterial pressuredetection chamber 2122 is located prior to the pump rotor. That is, thearterial pressure detection chamber 2122 is arranged to facilitatemeasuring pre-pump arterial pressure. Additionally or alternatively, insome embodiments, pressure can be measured post-pump (but prior to thehollow fibers). The pressure detection chambers 2122 and 2142 are eachconfigured to interface with a respective pressure transducer of thetreatment module 220.

The dialyzer 2100 is configured to receive dialysate, and to direct thedialysate to flow through the housing 2110. For example, in the depictedembodiment, the second end cap 2140 defines a dialysate inlet port 2149and the first end cap 2120 defines a dialysate outlet port 2125. Thedialysate flows into the second end cap 2140 via the dialysate inletport 2149, and then enters the middle housing portion 2112 containingthe bundle of hollow fibers 2114. The dialysate flows through the middlehousing portion 2112 via the spaces defined between the outer diametersof the fibers of the bundle of hollow fibers 2114. In other words, whilethe blood flows within the lumens of the fibers of the bundle of hollowfibers 2114, the dialysate liquid flows along the outsides of thefibers. The semi-permeable walls of the fibers of the bundle of hollowfibers 2114 separate the dialysate liquid from the blood. The dialysateliquid flows out of the middle housing portion 2112 and into the firstend cap 2120. The dialysate liquid exits the first end cap 2120 via thedialysate outlet port 2125.

Referring to FIGS. 40 and 41 , an alternative second (venous) end cap600 can be used with any of the dialyzers described herein. The venousend cap 600 is configured with particular features to encourageseparation of gases such as air from the extracorporeal circuit duringpriming and during use. The venous end cap 600 includes a spiral inletlumen 610 (or spiral lumen 610), an outlet 620, an angled baffle 630, adome 640, an air purge member 650, and a chamber 660. In FIG. 41 , thedome 640 and air purge member 650 are not shown in order to providebetter visibility of the structures inside of the chamber 660. An upperportion of the venous end cap 600 comprises the dome 640 and theattached air purge member 650. A lower or bottom portion of the venousend cap 600 defines the spiral inlet lumen 610 and its outlet 620, andcomprises the angled baffle 630. The spiral inlet lumen 610 and theangled baffle 630 can be integrally formed with the lower portion of thevenous end cap 600. The outlet of the spiral inlet lumen 610 is locatedbetween the upper portion of the venous end cap 600 and the outlet 620of the chamber 660.

In use, blood exits the lumens of the hollow fibers and flows to thechamber 660 via an inlet to the spiral inlet lumen 610 and by the spiralinlet lumen 610 itself. In other words, the spiral inlet lumen 610provides fluid communication between the chamber 660 and areas exteriorto the chamber 660. The inlet to the spiral inlet lumen 610 isconfigured on the bottom side of the bottom portion of the venous endcap 600. The inlet to the spiral inlet lumen 610 has a larger area thana transverse cross-section of the spiral inlet lumen 610. The outlet ofthe spiral inlet lumen 610 is configured on the upper side of the bottomportion. The spiral inlet lumen 610 extends from the lower portion ofthe venous end cap 600 and spirals vertically toward the upper portionof the venous end cap 600 (toward the dome 640). The spiral inlet lumen610 is configured so that the blood entering the chamber is flowingessentially horizontally (i.e., transverse to the longitudinal axis ofthe dialyzer). The outlet of the spiral inlet lumen 610 (i.e., where thespiral inlet lumen 610 terminates within the chamber 660) is near to theperipheral wall of the chamber 660. In other words, the outlet of thespiral inlet lumen 610 is offset from the central axis of the dialyzerand of the venous end cap 600 itself. Accordingly, blood flowing intothe chamber 660 may tend to impact the peripheral wall of the chamber660, which will engender a spiral flow path to the blood.

The angled baffle 630 is located adjacent to the outlet of the spiralinlet lumen 610, such that blood exiting the spiral inlet lumen 610 willtend to impact on the angled baffle 630 and be deflected upward towardthe dome 640, which is a rigid portion of the housing such that itdefines the fixed shape of the upper portion of the chamber 660. Theimpact surface of the angled baffle 630 can be angled at an acute anglein relation to the essentially horizontal blood flow direction as theblood exits the spiral inlet lumen 610. For example, in some embodimentsthe angle of the angled baffle 630 relative to horizontal, and/orrelative to the central longitudinal axis of the dialyzer and venous endcap 600, is in a range of 10° to 70°, or 20° to 60°, or 30° to 50°, or30° to 40°, without limitation.

The air purge member 650 allows air and other gases to exit the venousend cap 600 while preventing fluids such as blood from exitingtherethrough. The air purge member 650 can also be used as an accessport. That is, the air purge member 650 can be configured for uses suchas sample extraction and administration of medicaments (e.g., heparin).

To perform optimally as an air separator during use, the venous end cap600 needs to be substantially cleared of air by priming prior to thestart of a blood treatment. That is, sufficient air needs to be clearedfrom the chamber 600 during the priming phase for the chamber 660 to beoptimally effective for separating air later on during the bloodtreatment. During priming, it is intended that air in the chamber 660 issubstantially flushed out of the chamber 660 by a priming solution. Byvirtue of the velocity and directional flow engendered by the structureof the venous end cap 600, the efficacy of the priming solution toremove air from the chamber 660 is enhanced (e.g., with air flushed outthrough a rinse port positioned on the blood treatment machine).Otherwise, air remaining in the chamber 660 can also be manually removedvia the air purge member 650 by connecting a syringe to the air purgemember 650, for example.

During use, the flow velocity engendered by the structure of the venousend cap 600 presents a challenge for air separation as air in the bloodneeds time to be influenced by the forces of gravity and can remaintrapped in the blood. The structure of the venous end cap 600 causes acircular, spiral-like flow that can act to slow the velocity of bloodflow. Accordingly, air tends to migrates toward the center of the spiralflow where velocity is the lowest, and where effects of gravity havetime to act on the air so that it can separate from the blood and becollected at the top of the dome 640.

While the structures of the venous end cap 600 that function to deaerateliquids are described above in the context of an end cap of a dialyzer,it should be understood that the structures for deaeration can beincorporated in conjunction with various other types of devices, or as adeaeration device to itself. That is, the structures for deaeration ofthe venous end cap 600 can be incorporated as portions of a deaerationchamber that can be implemented in a wide variety of suitableembodiments. Additionally, while the venous end cap 600 is primarilyintended to deaerate blood, priming solution, or other medical liquids,it should be understood that the structures for deaeration of the venousend cap 600 can be implemented in other embodiments so as to deaerateother types of liquids.

Referring to FIGS. 42-44 , another alternative second (venous) end cap700 can be used with any of the dialyzers described herein. The venousend cap 700 is configured with particular features to encourageseparation of gases such as air from the extracorporeal circuit duringpriming and during use.

The venous end cap 700 includes an upper or top portion comprising adome 710 and an attached air purge member 730 (shown in FIG. 43 , butnot shown in FIGS. 42 and 44 ). The venous end cap 700 includes a loweror bottom portion comprising an inlet passage member 740, and defining achamber outlet 750 (FIG. 44 ). A chamber 720 is defined between theupper and lower portions of the venous end cap 700.

The inlet passage member 740 comprises a projection extending axiallyfrom the bottom portion of the venous end cap 700 along a central axis(e.g., longitudinal axis) of the venous end cap 700 (and a dialyzer as awhole). The inlet passage member 740 can be integrally formed with thelower portion of the venous end cap 700. The outlet of the inlet passagemember 740 is at a terminal end of the projection, elevated above thechamber outlet 750, and elevated above a middle elevation of the chamber720. The outlet of the inlet passage member 740 is radially offset fromthe central axis (e.g., longitudinal axis) of the venous end cap 700(and a dialyzer as a whole). The dome 710 is a rigid upper portion ofthe housing such that it defines the fixed shape of the upper portion ofthe chamber 720.

The blood after being treated by the hollow fiber membrane enters thechamber 720 of the venous end cap 700 though the inlet passage member740 formed in the axial middle of the venous end cap 700. An outlet endportion at the terminal end of the inlet passage member 740 isconfigured spirally (e.g., with a beveled surface, at an acute anglerelative to the central axis, along which the blood exiting the inletpassage member 740 will flow). Accordingly, the outlet end portion atthe terminal end of the inlet passage member 740 is configured toengender a spiral component to the flow path of the blood as it exitsthe inlet passage member 740 to enter the chamber 720. The blood entersthe chamber 720 after spilling over from the terminal outlet end portionof the inlet passage member 740. The blood can be degassed by means ofgravity (bubbles will tend to rise in relation to the blood and toseparate from the blood) as it flows in a thin layer, and with a spiralflow, into the chamber 720 from the end portion of the inlet passagemember 740 and toward the chamber outlet 750.

While the depicted embodiment the middle inlet passage member 740 onlyincludes one spiral-channel outlet of the inlet passage member 740 (toenter the chamber 720), in some embodiments the inlet passage member 740could include multiple spiral-channel outlets. In some of thoseembodiments, the multiple spiral-channel outlets can be symmetrically orevenly distributed in the venous end cap 700 so as to minimizeturbulence in the blood and to balance the flow symmetrically within thechamber 720.

While the structures of the venous end cap 700 that function to deaerateliquids are described above in the context of an end cap of a dialyzer,it should be understood that the structures for deaeration can beincorporated in conjunction with various other types of devices, or as adeaeration device to itself. That is, the structures for deaeration ofthe venous end cap 700 can be incorporated as portions of a deaerationchamber that can be implemented in a wide variety of suitableembodiments. Additionally, while the venous end cap 700 is primarilyintended to deaerate blood, priming solution, or other medical liquids,it should be understood that the structures for deaeration of the venousend cap 700 can be implemented in other embodiments so as to deaerateother types of liquids.

Referring to FIGS. 45-47 , another alternative second (venous) end cap800 can be used with any of the dialyzers described herein. The venousend cap 800 is configured with particular features to encourageseparation and collection of gases, such as air, from the extracorporealcircuit. For example, the venous end cap 800 includes a reconfigurablepopper cap, as described further below.

The venous end cap 800 includes one or more peripheral inlets 810 (or aplurality of peripheral inlets 810), an outlet 820, a reconfigurabledome 840 (or flexible dome), an air purge member 850, and a chamber 860.In FIG. 47 , the dome 840 and air purge member 850 are not shown inorder to provide better visibility of the structures inside of thechamber 860. In FIG. 45 , the reconfigurable dome 840 is in a first,inverted configuration such that the chamber 860 essentially does notexist, or only minimally exists. In FIG. 46 , the reconfigurable dome840 is in a second, domed configuration such that the chamber 860 isdefined. The chamber 860 is larger when the reconfigurable dome 840 isin the second configuration as compared to the first configuration.

The one or more of peripheral inlets 810 are passageways that allowliquid exiting from the hollow fibers of the dialyzer to enter thechamber 860. After entering the chamber 860, the liquid dwells for atime in the chamber 860 and then exits the chamber 860 via the outlet820. The outlet 820 is in the side wall of a lower portion of thehousing and at a lower elevation than the one or more peripheral inlets810. Said another way, the when the reconfigurable dome 850 is in thesecond, domed configuration, the outlet 820 is on an opposite side ofthe one or more peripheral inlets 810 in comparison to thereconfigurable dome 850.

In some embodiments, the outlet 820 is positioned at other locations.For example, in some embodiments the outlet 820 is positioned at thecenter and bottom of the concave lower portion of the chamber 860, asdepicted by an outlet 820′ shown in FIG. 47 . In this location, theoutlet 820′ is surrounded by the one or more peripheral inlets 810 andequidistant from each inlet of the one or more peripheral inlets 810. Insome embodiments, multiple outlets are included. For example, in someembodiments the outlet 820 and the outlet 820′ are each included in asingle embodiment.

In some embodiments, there are multiple peripheral inlets 810 (e.g., sixin the depicted embodiment) spaced apart from each other around theperiphery of the chamber 860 so that the liquid (e.g., priming solution,blood, etc.) entering the chamber 860 does so at a low velocity. Bymaintaining a low liquid flow velocity in the chamber 860, more time isallowed for air in the liquid to rise (i.e., to separate from theliquid) due to the effects gravity. However using this low velocityapproach tends to make flushing air from a conventional chamber in aconventional end cap during the priming phase more difficult. Thespecial popper cap (i.e., the reconfigurable dome 840) of the venous endcap 800 helps to mitigate this issue.

The reconfigurable dome 840 (or flexible dome 840) is a hemi-sphericalmember made of a semi-flexible material. The natural, least stressedconfiguration of the reconfigurable dome 840 is the shape shown in FIG.46 (the dome shape, domed configuration, or the second configuration).The second configuration (domed shape) of the reconfigurable dome 840 isa more stable configuration than the first configuration (invertedconfiguration). However, the reconfigurable dome 840 will also maintainits inverted configuration shown in FIG. 45 . The inverted configurationis the initial configuration of the reconfigurable dome 840 (i.e., theconfiguration of the reconfigurable dome 840 prior to priming or use).The reconfigurable dome 840 (or flexible dome 840) will reconfigurationfrom the first configuration (inverted configuration) to the secondconfiguration (domed configuration) in response to pressurization withinthe chamber 860.

During priming, as liquid passes through the one or more inlets 810, theliquid will apply forces to the inner surface of the invertedreconfigurable dome 840. The reconfigurable dome 840 will begin todeflect upward in response to the forces of the liquid, and the chamber860 will thereby begin to form. When the reconfigurable dome 840 hasdeflected upward to threshold extent, the reconfigurable dome 840 willnaturally tend to break through or pop open toward the domeconfiguration shown in FIG. 46 in which the chamber 860 is fully formed.Advantageously, because the chamber 860 essentially does not exist, oronly minimally exists, during initial priming, there is essentially noair that needs to be flushed out by the liquid priming process. However,after the chamber 860 has been formed, the chamber 860 functions toseparate air/gas from the blood during use.

While the structures of the venous end cap 800 that function to deaerateliquids are described above in the context of an end cap of a dialyzer,it should be understood that the structures for deaeration can beincorporated in conjunction with various other types of devices, or as adeaeration device to itself. That is, the structures for deaeration ofthe venous end cap 800 can be incorporated as portions of a deaerationchamber that can be implemented in a wide variety of suitableembodiments. Additionally, while the venous end cap 800 is primarilyintended to deaerate blood, priming solution, or other medical liquids,it should be understood that the structures for deaeration of the venousend cap 800 can be implemented in other embodiments so as to deaerateother types of liquids.

Multiple differing types of dialyzer venous end caps with structures fordeaerating liquids are described above (e.g., venous end cap 600, venousend cap 700, and venous end cap 800). It should be understood thatfeatures of the various venous end caps 600, 700, and/or 800 can bemixed, combined, added on, substituted for other features, and the likeso, as to create hybrid designs that are within the scope of thisdisclosure. For example, while the venous end cap 800 is described ashaving the reconfigurable dome 840, in some embodiments a rigid/fixeddome (e.g., the dome 640, or the dome 710) can be substituted for thereconfigurable dome 840. Conversely, while the venous end cap 600 andthe venous end cap 700 are described as having rigid/fixed domes, insome embodiments a reconfigurable dome (such as the reconfigurable dome840) can be substituted instead of the rigid/fixed domes. The inletand/or outlet configurations and/or locations of the various venous endcaps 600, 700, and/or 800 can also be substituted, or added, across thevarious designs. By way of these examples, it should be understood thatall possible hybrid designs using the features of the various venous endcaps 600, 700, and/or 800 are envisioned and within the scope of thisdisclosure.

The deaeration chambers described herein are designed to separate gases(e.g., air) from liquids (e.g., blood) by facilitating the gases thathave a lower density than liquids to naturally migrate upward toward thedomes of the deaeration chambers. Accordingly, it can be said that thedomes are, or comprise, the upper portion of the deaeration chambers.The end of the deaeration chamber that is opposite of the dome can bereferred to as the lower or bottom portion, or referred to as positionedbelow the dome. Hence, terms such as above, below, upper, lower, top,and bottom can be used to define particular portions, positions, ordirections in the context of the deaeration chambers described herein.Additionally, the dialyzers described herein can be configured forattachment to a blood treatment machine (e.g., the treatment module 220)such that the second end cap (venous end cap) is above the first end cap(arterial end cap).

The devices and methods described above are examples of the innovativeaspects disclosed herein. As described below, without limitation, otherembodiments and alternatives are also encompassed by the scope of thisdisclosure.

While the clamps 242 and 244 are described as functioning as on/offvalves, in some embodiments, the clamps 242 and 244 are used to variablymodulate the flow of blood through the arterial line 102 and/or thevenous line 104 (e.g., across a range of partially restricted clampsettings).

While the first end cap 120 and the second end cap 140 have beendescribed as having a particular arrangement of ports and pressurechambers, in some embodiments the end caps have other arrangements ofthe ports and pressure chambers.

While the treatment module 220 is described as being cantilevered fromthe blood treatment machine console 210 by the adjustable arm 280, insome embodiments the treatment module 220 is attached to the bloodtreatment machine console 210 by a pivot mechanism, directly attached,or integrated therein. In some such cases, the arterial line 102 and thevenous line 102 can be more than a meter in length.

While the dialyzer 100 has been described as having the integralpressure detection chambers 122 and 142, in some embodiments arterialand/or venous pressure detection is performed at positions along thearterial line 102 and/or the venous line 102 rather than at dialyzer100. In such a case, the pressure detection chambers 122 and/or 142 areeliminated from the dialyzer 100 (although the dialyzer 100 may stillinclude an integrated magnetic pump rotor, e.g., rotor 132 or rotor137).

While the dialyzer 100 has been described as having an integral magneticpump rotor (e.g., rotor 132 or rotor 137), in some embodiments aperistaltic pump acting on the arterial line 102 is included instead. Insuch a case, the rotor is eliminated from the dialyzer 100 (although thedialyzer 100 may still include the integrated pressure detectionchamber(s) 122 and/or 142). Some examples utilize other blood-pumpingmechanisms (e.g., diaphragm pumps, screw pumps, piston pumps,peristaltic pumps, and the like).

While components of the dialyzer 100 such as the magnetic pump rotor(e.g., rotor 132 or rotor 137) and the pressure detection chambers 122and 142 have been described as being integrated into the end caps 120and 140 of the dialyzer 100, in some embodiments one or more of suchcomponents can be integrated into portions of the dialyzer 100 otherthan the end caps 120 and 140.

While the blood flow path through the dialyzer 100 has been illustratedas proceeding upward from the first end cap 120 at the bottom of thedialyzer 100 to the second end cap 140 at the top of the dialyzer 100,in some embodiments the blood flow path through the dialyzer 100 canproceed downward from the second end cap 140 at the top of the dialyzer100 to the first end cap 120 at the bottom of the dialyzer 100. In sucha case, in some embodiments the integrated magnetic pump rotor can belocated in the second end cap 140 at the top of the dialyzer 100.

While some examples include a treatment module 220 that is cantileveredfrom a blood treatment machine console 210 by an arm 280, it should beunderstood that other examples have these components integrated as asingle unit in a shared housing. Moreover, some examples have atreatment module that is not mechanically supported by the console. Forexample, some have treatment modules that are mounted to anotherstructure (e.g., a wall or wall bracket, or a floor stand), or which areto be placed on a surface, such as a desk or table. Such examples mayinclude flexible fluid tubes and electrical cables between the modulesand consoles to transfer fluids and electricity/signals. Other exampleshave treatment modules that can receive power separately from theconsole and/or have wireless communication channels with the console.

While deaeration chambers have been described in the context of venousend caps of dialyzers, the deaeration chamber concepts can also beimplemented in the context of standalone medical fluid deaerationchamber devices, apart from dialyzers, or as a part of any othersuitable fluid handling device.

A number of embodiments of the invention have been described.Nevertheless, it will be understood that various modifications may bemade without departing from the spirit and scope of the invention.Accordingly, other embodiments are within the scope of the followingclaims.

What is claimed is:
 1. A dialyzer comprising: an elongate housingdefining a longitudinal axis and including first and second end caps atopposite ends of the housing; and a bundle of hollow membranous fiberswithin an interior of the housing between the first and second end caps,each of the hollow membranous fibers defining a lumen, wherein thedialyzer defines a blood flow path that extends through the first endcap, then through the lumens of the hollow membranous fibers, and thenthrough the second end cap, wherein the blood flow path enters the firstend cap transverse to the longitudinal axis, then extends longitudinallytoward the bundle of hollow membranous fibers and longitudinally throughopenings at locations defined by the first end cap prior to entering thelumens of the hollow membranous fibers, and wherein the locations of theopenings are biased toward radially outer annular portions of the bundlesuch that, when blood flows through the openings and along the bloodflow path, the blood flow to the radially outer annular portions of thebundle is increased relative to a central portion of the bundle.
 2. Thedialyzer of claim 1, wherein a portion of the blood flow path within thefirst end cap extends transverse to the longitudinal axis.
 3. Thedialyzer of claim 2, wherein the blood flow path within the first endcap also includes blood flow path portions that extend in oppositedirections along the longitudinal axis.
 4. The dialyzer of claim 3,wherein the first end cap redirects the blood flow path that extendstransverse to the longitudinal axis to extend parallel to thelongitudinal axis toward the bundle of hollow membranous fibers.
 5. Thedialyzer of claim 1, wherein the first end cap defines a toroidal space.6. The dialyzer of claim 1, wherein the first end cap defines at leasttwo of the openings.
 7. The dialyzer of claim 1, wherein the blood flowpath enters the first end cap between the openings and the bundle ofhollow membranous fibers.
 8. The dialyzer of claim 1, further comprisinga check valve along the blood flow path.
 9. The dialyzer of claim 1,wherein the second end cap includes a port along the blood flow path foradministering medicaments or extracting a fluid sample.
 10. The dialyzerof claim 1, wherein the housing further comprises a deaeration chamberalong the blood flow path.
 11. The dialyzer of claim 10, wherein thedeaeration chamber is defined in the second end cap.
 12. The dialyzer ofclaim 1, wherein the openings comprise at least two arcuate slots. 13.The dialyzer of claim 1, wherein the openings comprise at least fourarcuate slots.
 14. A dialyzer comprising: an elongate housing defining alongitudinal axis and including first and second end caps at oppositeends of the housing; and a plurality of hollow membranous fibers withinan interior of the housing between the first and second end caps, eachof the hollow membranous fibers defining a lumen, wherein the dialyzerdefines a blood flow path that extends through the first end cap, thenthrough the lumens of the hollow membranous fibers, and then through thesecond end cap, wherein the blood flow path enters the first end captransverse to the longitudinal axis, then extends toward the hollowmembranous fibers and through openings defined by the first end capprior to entering the lumens of the hollow membranous fibers, andwherein the blood flow path enters the first end cap between theopenings and the hollow membranous fibers.
 15. The dialyzer of claim 14,wherein the blood flow path within the first end cap also includes bloodflow path portions that extend in opposite directions along thelongitudinal axis.
 16. The dialyzer of claim 14, wherein the first endcap defines a toroidal space and at least two of the openings.
 17. Thedialyzer of claim 14, wherein the openings comprise at least two arcuateslots.
 18. The dialyzer of claim 14, wherein the openings are biasedtoward outer annular portions of the plurality of hollow membranousfibers such that, when blood flows along the blood flow path, the bloodflow to the outer annular portions is increased relative to a centralportion of the plurality of hollow membranous fibers.
 19. The dialyzerof claim 14, further comprising a deaeration chamber defined in thesecond end cap.
 20. The dialyzer of claim 19, wherein the second end capincludes a port along the blood flow path for administering medicamentsor extracting a fluid sample.